Department of Research & Evaluation News

Taking doxycycline after sex helped prevent chlamydia and syphilis, but its ability to prevent gonorrhea faded over time as drug‑resistant strains became more common, according to new research. The findings show both the benefits and limits of a prevention strategy now widely used by patients, clinicians, and public health programs to prevent sexually transmitted infection (STI) outbreaks among men who have sex with men.

The study focused on doxycycline post‑exposure prophylaxis, or DoxyPEP, was published in May, 2026, in The Lancet Infectious Diseases.

“This study shows that prevention tools can be powerful, but they are not one‑size‑fits‑all,” said the study’s co-senior author, Sara Y. Tartof, PhD, MPH, n infectious disease epidemiologist with the Kaiser Permanente Southern California Department of Research & Evaluation. “Doxycycline after sex can still help protect people from some infections, but rising antibiotic resistance means we have to keep watching closely, adjusting strategies, and doctors need to be clear with patients about what it can and cannot do over time.”

Kaiser Permanente Southern California researchers teamed up with University of California, Berkeley researchers and others on this retrospective observational study using electronic health records of patients receiving care from Kaiser Permanente Southern California between January 2023 and June 2025.

Researchers reviewed medical records from 26,582 men who have sex with men, and transgender women, who were living with HIV or using HIV prevention medication and had at least one test for a STI during the study period. The analysis spanned the months before and after California issued statewide guidance recommending DoxyPEP in April 2023.

Researchers assessed how DoxyPEP reduced chlamydia, gonorrhea, and syphilis infections over time and whether its effectiveness changed as antibiotic resistance increased in the region. Within 90 days of receiving a prescription, chlamydia infections were reduced by about two‑thirds and syphilis infections by more than half, with protection against both infections remaining evident more than two years after implementation.

Protection against gonorrhea, however, declined steadily and was no longer observed within about one year of widespread use. Early in the study period, gonorrhea infections were reduced by more than 40%, but by 2025 no measurable benefit was observed as antibiotic‑resistant strains became more common. During the same period, chlamydia diagnoses declined by about 67% and syphilis diagnoses by about 49%, while gonorrhea diagnoses declined by only about 13%, mirroring the loss of preventive effect.

Earlier studies and clinical trials suggested doxycycline post‑exposure prophylaxis could reduce chlamydia and syphilis infections, while evidence for gonorrhea prevention was mixed, particularly in geographic regions with existing antibiotic resistance. This research adds to the literature by showing how this widely used prevention strategy performs over time in everyday clinical care, rather than under controlled trial conditions. For clinicians and public health officials, the study underscores the need to tailor prevention strategies by infection type, to closely monitor antimicrobial resistance, and to balance the benefits of reducing some STIs with the risks posed by rising antibiotic resistance.

In addition to Dr. Tartof, other researchers on this study include lead author Matan Yechezkel, PhD, and co-senior author Joseph A. Lewnard, PhD of University of California, Berkeley; David Helekal, PhD, and Yonatan H. Grad, MD, of Harvard University: Banshri Kapadia, MS; Vennis Hong, MPH; Magdalena E. Pomichowski, MPH; Iris Anne C. Reyes, MPH, and Gregg S. Davis, PhD, of the Department of Research & Evaluation; and Nicola F. Müller, PhD, of University of California, San Francisco